1. Field of the Invention.
The invention relates to a rack system for a plurality of specimen containers for use in performing assays such as chemo- or bioluminescence measurements in a measuring instrument in which, after procedures have been performed, the specimen containers in the rack are moved successively past a measurement site.
2. Prior Art.
Assays, such as measurements of chemiluminescence or bioluminescence, have gained considerable significance for the discovery or identification of certain substances, particularly in the medical field. Specialized techniques known as immunoassays are used for this purpose, based on the fact that for each of these substances (antigens, such as endogenous hormones or disease-causing microorganisms), a specific antibody can be associated with it, which may be present in the form of an endogenous immune substance or may be produced artificially. With the antigen to be detected, such a specific antibody forms a complex; if the antibody in turn is provided with a detectable marking, or label, then the presence of the applicable antigen can be detected by detecting this marking. The labeled antibody accordingly serves in a practical sense as a measuring sensor. Depending on the type and structure of the antigen and associated antibody, various immunoassays have been developed, which differ in the production of the thus-labeled antigen-antibody complex; an example is immunometric assays (for instance for detecting the TSH antigen), in which the antigen to be detected is first coupled to the associated, unlabeled antibody and subsequently the associated labeled antibody is coupled in turn to the antigen, forming a sandwich structure, with the result that the number of labels is approximately in proportion to the number of existing antigens to be detected.
This is contrasted by competitive assays, in which the antigens to be detected couple, in competition with labeled antigens, to a limited number of antibodies; the eventual result is that the number of labels decreases with the number of antigens to be detected.
Nonradioactive substances that can be induced to luminescence, such as acridinium ester molecules, have been increasingly used for the labeling, in which an exothermic reaction is initiated in the presence of hydrogen peroxide in alkaline solution, and the thermal energy of the reaction leads initially to the formation of excited molecular states; from these excited quantum states, the molecules then return (possibly with intermediate stops in between) to their basic state, and the energy difference between the quantum states is liberated in the form of photons, which can finally then be detected with the aid of a photomultiplier.
If such a label is used in immunoassays, such tests are consequently called chemiluminescence immunoassays. The basic features and details of such tests are explained for instance in the Journal of Clinical Immunoassays. Vol. 7, No. 1, 1984, pp. 82 ff, or Methods of Enzymology, Vol. 133, Part B, pp. 366 ff.
A common feature of all these immunoassays is that to perform them, a more or less large number of method steps is needed to achieve buildup of the aforementioned complex, that includes the label, from the specimen taken from the patient in which the applicable substance is to be detected. This takes place in stages including, among other steps, addition of the labeled antibodies or antigens, elimination of excess substances, and so forth.
As a rule, such measurement techniques are not performed, on a commercial laboratory scale, "individually", that is, by successive processing of a single specimen container; instead, batch quantities of up to a 100 sample containers are typical. The problem consequently arises of how to make a large number of sample containers, as a rule test tubes, proceed quickly and reliably, without any change in their order, through these method steps. Between method steps, the specimen containers must be shifted repeatedly among the various pieces of equipment involved, and finally must be moved into the measuring instrument.
It is accordingly typical for the specimen containers, optionally after suitable pretreatment, used for performing this kind of measurement, which is composed of a plurality of method steps, to be kept in a rack while as many method steps as possible can be carried out. In the simplest case, such a rack comprises a plastic stand having, for instance, a matrix of 5.times.10 holes on its top, into which the specimen containers are inserted.
For performing the actual measurement with a plurality of such test tubes, use may be made of a generic holder system for successive measurement of radioactively labeled specimens, such as described in U.S. Pat. No. 4,029,961. This system uses the so-called horizontal paternoster principle, in which a number of support elements, each holding a plurality of specimen containers, are moved successively past the measuring site. A holder that accommodates a plurality of specimen containers in a row is mounted on each support element. The specimen containers are retained by elastic plastic tongues of the holder until they reach the measuring position where the plastic tongues release the particular specimen container to be measured and that specimen container is then shifted vertically out of its holder to the actual measuring position.
German Published, Non-Examined patent application No. 25 29 071 shows a similar apparatus, in which plastic tongues extend under the bottom of the specimen containers. Because of the necessity of removing the specimen containers from their holders in their measuring position, this apparatus is necessarily complicated in structure and can be used only along with a support element adapted to it.
In the use of this rack system, the shifting of the specimen containers from the racks into the holders accordingly presents problems in that it is very time-consuming and is subject to mistakes caused by human error; particularly when such measuring methods are used in the medical field, such mistakes may possibly have grave consequences for the patient involved if there is an inaccurate diagnosis.
In another measuring instrument, disclosed in German Published, Non-Examined patent application No. 36 23 601, the specimen containers are inserted into holders placed against one another like links in a chain, which are moved continuously past the measuring site of the measuring instrument. Here the holders have lateral measuring openings, so that even in their respective measuring position the specimen containers can remain in the holders; although this arrangement allows structural simplification of the retaining tongues compared with the above-described systems, it is still unfeasible in the final analysis, because the holders themselves simultaneously also serve as the support element for carrying the specimen containers through the measuring instrument, and consequently must have a complicated structure. Hence the fundamental problem is still not solved; once again the specimen containers must be inserted individually into the holders and removed from them again after the measurement, since on the one hand the holders are too complicated and therefore too expensive to throw away, but on the other hand are difficult to clean.
A system in which the specimen containers can remain in position during the measurement and in which a separate support element on which the specimen containers can be mounted is used is disclosed in
Published European Patent Document No. 0 039 145. In this system, however, clearly the advantage of ease attained because specimen containers need not be removed for the measurement procedure, is achieved at the cost of integrating 3.times.3 cuvettes into each holder, which means that once again the holders can necessarily be used only with a specific measuring instrument or support element designed for them. Moreover, the aforementioned advantage is due to the fact that measurement in the measuring instrument is performed vertically rather than horizontally; aside from the basic disadvantages of this measuring method, including a long path of radiation, and scattering effects caused by the bottom of the specimen containers, it is not possible to add reagents directly prior to the measurement, i.e., in the measuring position, because the space above the opening of the specimen containers is necessarily "occupied" by the detector head.
Accordingly this apparatus of European Patent Document No. 0 039 145 is not usable for measurements of the kind that require such an addition of reagents, or in other words for the immunoassays described at the outset above, where the luminescence of the label must be initiated immediately prior to the measurement. The resultant necessity for horizontal measurement, for which purpose the lateral measurement openings are provided in the manner disclosed in German Published, Non-Examined patent application No. 36 23 601, also precludes the use of holders having a matrix-like structure.
The system of European Patent Document No. 0 039 145 is therefore unusable for chemiluminescence and bioluminescence measurement.
German Published, Non-Examined patent application No. 24 48 658 discloses a holder for specimen containers that is intended both for holding a plurality of specimen containers and for passing them through the measurement site; similarly to the aforementioned German Published, Non-Examined patent application No. 36 23 601, this "integrated" version necessarily has a complicated structure, and consequently once again the specimen containers must be inserted individually for measurement and then removed again. In the measurement per se, specimens are aspirated from the test tubes; consequently no assays are performed. Since the holders have laterally closed receiving channels for the specimen containers, known as "holder pockets", the lateral openings or "holes" shown being intended not for measuring the specimens but rather solely for identifying individual holders using an optical reader, these holders are likewise unsuitable for performing chemiluminescence or bioluminescence measurements.